Protein kinases controlling the onset of mitosis

Ferrari, Stefano

doi:10.1007/s00018-005-5515-3

Cited by 53 publications

(46 citation statements)

References 190 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…21). Likewise, the initial Golgi ribbon unlinking at late G 2 /early prophase, as well as its subsequent unstacking and vesiculation, depend on the phosphorylation of Golgi-localized proteins by several kinases (reviewed in refs.…”

Section: Kinase-mediated Regulation Of the Two-step Mitotic Golgi Framentioning

confidence: 99%

“…CDK1 is the central regulator of many aspects of the cell entry and progression through mitosis. 21 However, regarding the mitotic Golgi disassembly, it appears to act after MEK1/ERK-mediated ribbon unlinking to promote the complete vesiculation of the Golgi stack. 22,25 This effect is likely due to the cessation of ER-Golgi and intra-Golgi transport that is observed in metaphase leading partly to an accumulation of COPI vesicles.…”

Section: Kinase-mediated Regulation Of the Two-step Mitotic Golgi Framentioning

confidence: 99%

See 1 more Smart Citation

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Rabouille¹,

Kondylis²

2007

Cell Cycle

View full text Add to dashboard Cite

Cell cycle checkpoints have been associated mostly with signaling mechanisms monitoring the genetic material for abnormalities and inaccuracy in partitioning, such as DNA lesions or failure in chromosome attachment to kinetochores. However, it becomes more evident that other checkpoints are turned on by cytoplasmic events, such as the cytoskeleton organization and the organelle structure. Here, we summarize recent evidence strongly suggesting that the integrity of the Golgi ribbon and more precisely the tubules interconnecting the Golgi stacks to form this ribbon, at late G 2 /early prophase, is linked to a Golgi-related G 2 /M checkpoint. A number of kinases phosphorylating a small subset of Golgi-localized proteins have been shown to promote the G 2 -specific Golgi ribbon unlinking, allowing the cell to enter mitosis. When these kinases are inactivated or when the substrates cannot be phosphorylated, Golgi unlinking is prevented and the cells are blocked or delayed in G 2 phase.

show abstract

Section: Kinase-mediated Regulation Of the Two-step Mitotic Golgi Framentioning

confidence: 99%

Section: Kinase-mediated Regulation Of the Two-step Mitotic Golgi Framentioning

confidence: 99%

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Rabouille¹,

Kondylis²

2007

Cell Cycle

View full text Add to dashboard Cite

show abstract

“…32 We have previously shown that AurA, which controls ploidy by ensuring spindle bi-polarity, 33 is inhibited in response to the generation of double strand breaks in G 2 . 16 In the present study we addressed the molecular mechanism by which DNA damage response pathways restrain AurA activity.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 In most kinases, phosphorylation of the T-loop site is of key importance for supporting enzymatic activity. 32,34 The concomitant rapid activation of PP1 observed in irradiated cells led us to hypothesize an involvement of TPX2 in the mechanism of AurA inhibition by DNA damage. This reasoning was based on published evidence according to which physical interaction between AurA and TPX2 not only facilitates activation of the kinase 22 but additionally protects the T-loop site T 288 of activated AurA from dephosphorylation by PP1.…”

Section: Discussionmentioning

confidence: 99%

Mitotic DNA damage targets the Aurora A/TPX2 complex

Bhatia

Menigatti²,

Brocard³

et al. 2010

Cell Cycle

View full text Add to dashboard Cite

“…39,40 The activation of Aurora kinases involves de novo phosphorylations, and, in the case of Cdk1 activation, the removal of an inhibitory phosphate group on Tyr-15 by the phosphatase Cdc25B is required. 41 We monitored these events using phosphospecific antibodies that detect activation-specific phosphorylation of Aurora kinases and the state of Cdk1-Tyr-15 phosphorylation.…”

confidence: 99%

The IKK Inhibitor BMS-345541 Affects Multiple Mitotic Cell Cycle Transitions

Blažková

Schubert²,

Mikule³

et al. 2007

Cell Cycle

View full text Add to dashboard Cite

The IκB kinase (IKK) complex controls processes such as inflammation, immune responses, cell survival and the proliferation of both normal and tumor cells. By activating NFκB, the IKK complex contributes to G 1 /S transition and first evidence has been presented that IKKα also regulates entry into mitosis. At what stage IKK is required and whether IKK also contributes to progression through mitosis and cytokinesis, however, has not yet been determined. In this study, we use BMS-345541, a potent allosteric small molecule inhibitor of IKK, to inhibit IKK specifically during G 2 and during mitosis. We show that BMS-345541 affects several mitotic cell cycle transitions, including mitotic entry, prometaphase to anaphase progression and cytokinesis. Adding BMS-345541 to the cells released from arrest in S-phase blocked the activation of Aurora A, B and C, Cdk1 activation and histone H3 phosphorylation. Additionally, treatment of the mitotic cells with BMS-345541 resulted in precocious cyclin B1 and securin degradation, defective chromosome separation and improper cytokinesis. BMS-345541 was also found to override the spindle checkpoint in nocodazole-arrested cells. In vitro kinase assays using BMS-345541 indicate that these effects are not primarily due to a direct inhibitory effect of BMS-345541 on mitotic kinases such as Cdk1, Aurora A or B, Plk1 or NEK2. This study points towards a new potential role of IKK in cell cycle progression. Since deregulation of the cell cycle is one of the hallmarks of tumor formation and progression, the newly discovered level of BMS-345541 function could be useful for cell cycle control studies and may provide valuable clues for the design of future therapeutics.

show abstract

Protein kinases controlling the onset of mitosis

Cited by 53 publications

References 190 publications

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Mitotic DNA damage targets the Aurora A/TPX2 complex

The IKK Inhibitor BMS-345541 Affects Multiple Mitotic Cell Cycle Transitions

Contact Info

Product

Resources

About

Protein kinases controlling the onset of mitosis

Cited by 53 publications

References 190 publications

Golgi Ribbon Unlinking: An Organelle-Based G2/M Checkpoint

Golgi Ribbon Unlinking: An Organelle-Based G2/M Checkpoint

Mitotic DNA damage targets the Aurora A/TPX2 complex

The IKK Inhibitor BMS-345541 Affects Multiple Mitotic Cell Cycle Transitions

Contact Info

Product

Resources

About

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint